Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing

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Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing. / Karunakaran, Mohindar M.; Willcox, Carrie R.; Salim, Mahboob; Paletta, Daniel; Fichtner, Alina S.; Noll, Angela; Starick, Lisa; Nöhren, Anna; Begley, Charlotte R.; Berwick, Katie A.; Chaleil, Raphaël A.g.; Pitard, Vincent; Déchanet-merville, Julie; Bates, Paul A.; Kimmel, Brigitte; Knowles, Timothy J.; Kunzmann, Volker; Walter, Lutz; Jeeves, Mark; Mohammed, Fiyaz; Willcox, Benjamin E.; Herrmann, Thomas.

In: Immunity, Vol. 52, No. 3, 17.03.2020, p. 487-498.e6.

Research output: Contribution to journalArticle

Harvard

Karunakaran, MM, Willcox, CR, Salim, M, Paletta, D, Fichtner, AS, Noll, A, Starick, L, Nöhren, A, Begley, CR, Berwick, KA, Chaleil, RAG, Pitard, V, Déchanet-merville, J, Bates, PA, Kimmel, B, Knowles, TJ, Kunzmann, V, Walter, L, Jeeves, M, Mohammed, F, Willcox, BE & Herrmann, T 2020, 'Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing', Immunity, vol. 52, no. 3, pp. 487-498.e6. https://doi.org/10.1016/j.immuni.2020.02.014, https://doi.org/10.1016/j.immuni.2020.02.014

APA

Karunakaran, M. M., Willcox, C. R., Salim, M., Paletta, D., Fichtner, A. S., Noll, A., Starick, L., Nöhren, A., Begley, C. R., Berwick, K. A., Chaleil, R. A. G., Pitard, V., Déchanet-merville, J., Bates, P. A., Kimmel, B., Knowles, T. J., Kunzmann, V., Walter, L., Jeeves, M., ... Herrmann, T. (2020). Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing. Immunity, 52(3), 487-498.e6. https://doi.org/10.1016/j.immuni.2020.02.014, https://doi.org/10.1016/j.immuni.2020.02.014

Vancouver

Author

Karunakaran, Mohindar M. ; Willcox, Carrie R. ; Salim, Mahboob ; Paletta, Daniel ; Fichtner, Alina S. ; Noll, Angela ; Starick, Lisa ; Nöhren, Anna ; Begley, Charlotte R. ; Berwick, Katie A. ; Chaleil, Raphaël A.g. ; Pitard, Vincent ; Déchanet-merville, Julie ; Bates, Paul A. ; Kimmel, Brigitte ; Knowles, Timothy J. ; Kunzmann, Volker ; Walter, Lutz ; Jeeves, Mark ; Mohammed, Fiyaz ; Willcox, Benjamin E. ; Herrmann, Thomas. / Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing. In: Immunity. 2020 ; Vol. 52, No. 3. pp. 487-498.e6.

Bibtex

@article{b0a7525797824b0f864d6cbe93c283eb,
title = "Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing",
abstract = "Vγ9Vδ2 T cells respond in a TCR-dependent fashion to both microbial and host-derived pyrophosphate compounds (phosphoantigens, or P-Ag). Butyrophilin-3A1 (BTN3A1), a protein structurally related to the B7 family of costimulatory molecules, is necessary but insufficient for this process. We performed radiation hybrid screens to uncover direct TCR ligands and cofactors that potentiate BTN3A1's P-Ag sensing function. These experiments identified butyrophilin-2A1 (BTN2A1) as essential to Vγ9Vδ2 T cell recognition. BTN2A1 synergised with BTN3A1 in sensitizing P-Ag-exposed cells for Vγ9Vδ2 TCR-mediated responses. Surface plasmon resonance experiments established Vγ9Vδ2 TCRs used germline-encoded Vγ9 regions to directly bind the BTN2A1 CFG-IgV domain surface. Notably, somatically recombined CDR3 loops implicated in P-Ag recognition were uninvolved. Immunoprecipitations demonstrated close cell-surface BTN2A1-BTN3A1 association independent of P-Ag stimulation. Thus, BTN2A1 is a BTN3A1-linked co-factor critical to Vγ9Vδ2 TCR recognition. Furthermore, these results suggest a composite-ligand model of P-Ag sensing wherein the Vγ9Vδ2 TCR directly interacts with both BTN2A1 and an additional ligand recognized in a CDR3-dependent manner.",
keywords = "T cell receptor, Vγ9Vδ2, butyrophilin, complementarity-determining region, gamma delta T cell, ligand, phosphoantigen",
author = "Karunakaran, {Mohindar M.} and Willcox, {Carrie R.} and Mahboob Salim and Daniel Paletta and Fichtner, {Alina S.} and Angela Noll and Lisa Starick and Anna N{\"o}hren and Begley, {Charlotte R.} and Berwick, {Katie A.} and Chaleil, {Rapha{\"e}l A.g.} and Vincent Pitard and Julie D{\'e}chanet-merville and Bates, {Paul A.} and Brigitte Kimmel and Knowles, {Timothy J.} and Volker Kunzmann and Lutz Walter and Mark Jeeves and Fiyaz Mohammed and Willcox, {Benjamin E.} and Thomas Herrmann",
year = "2020",
month = mar,
day = "17",
doi = "10.1016/j.immuni.2020.02.014",
language = "English",
volume = "52",
pages = "487--498.e6",
journal = "Immunity",
issn = "1074-7613",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Butyrophilin-2A1 directly binds germline-encoded regions of the Vγ9Vδ2 TCR and is essential for phosphoantigen sensing

AU - Karunakaran, Mohindar M.

AU - Willcox, Carrie R.

AU - Salim, Mahboob

AU - Paletta, Daniel

AU - Fichtner, Alina S.

AU - Noll, Angela

AU - Starick, Lisa

AU - Nöhren, Anna

AU - Begley, Charlotte R.

AU - Berwick, Katie A.

AU - Chaleil, Raphaël A.g.

AU - Pitard, Vincent

AU - Déchanet-merville, Julie

AU - Bates, Paul A.

AU - Kimmel, Brigitte

AU - Knowles, Timothy J.

AU - Kunzmann, Volker

AU - Walter, Lutz

AU - Jeeves, Mark

AU - Mohammed, Fiyaz

AU - Willcox, Benjamin E.

AU - Herrmann, Thomas

PY - 2020/3/17

Y1 - 2020/3/17

N2 - Vγ9Vδ2 T cells respond in a TCR-dependent fashion to both microbial and host-derived pyrophosphate compounds (phosphoantigens, or P-Ag). Butyrophilin-3A1 (BTN3A1), a protein structurally related to the B7 family of costimulatory molecules, is necessary but insufficient for this process. We performed radiation hybrid screens to uncover direct TCR ligands and cofactors that potentiate BTN3A1's P-Ag sensing function. These experiments identified butyrophilin-2A1 (BTN2A1) as essential to Vγ9Vδ2 T cell recognition. BTN2A1 synergised with BTN3A1 in sensitizing P-Ag-exposed cells for Vγ9Vδ2 TCR-mediated responses. Surface plasmon resonance experiments established Vγ9Vδ2 TCRs used germline-encoded Vγ9 regions to directly bind the BTN2A1 CFG-IgV domain surface. Notably, somatically recombined CDR3 loops implicated in P-Ag recognition were uninvolved. Immunoprecipitations demonstrated close cell-surface BTN2A1-BTN3A1 association independent of P-Ag stimulation. Thus, BTN2A1 is a BTN3A1-linked co-factor critical to Vγ9Vδ2 TCR recognition. Furthermore, these results suggest a composite-ligand model of P-Ag sensing wherein the Vγ9Vδ2 TCR directly interacts with both BTN2A1 and an additional ligand recognized in a CDR3-dependent manner.

AB - Vγ9Vδ2 T cells respond in a TCR-dependent fashion to both microbial and host-derived pyrophosphate compounds (phosphoantigens, or P-Ag). Butyrophilin-3A1 (BTN3A1), a protein structurally related to the B7 family of costimulatory molecules, is necessary but insufficient for this process. We performed radiation hybrid screens to uncover direct TCR ligands and cofactors that potentiate BTN3A1's P-Ag sensing function. These experiments identified butyrophilin-2A1 (BTN2A1) as essential to Vγ9Vδ2 T cell recognition. BTN2A1 synergised with BTN3A1 in sensitizing P-Ag-exposed cells for Vγ9Vδ2 TCR-mediated responses. Surface plasmon resonance experiments established Vγ9Vδ2 TCRs used germline-encoded Vγ9 regions to directly bind the BTN2A1 CFG-IgV domain surface. Notably, somatically recombined CDR3 loops implicated in P-Ag recognition were uninvolved. Immunoprecipitations demonstrated close cell-surface BTN2A1-BTN3A1 association independent of P-Ag stimulation. Thus, BTN2A1 is a BTN3A1-linked co-factor critical to Vγ9Vδ2 TCR recognition. Furthermore, these results suggest a composite-ligand model of P-Ag sensing wherein the Vγ9Vδ2 TCR directly interacts with both BTN2A1 and an additional ligand recognized in a CDR3-dependent manner.

KW - T cell receptor

KW - Vγ9Vδ2

KW - butyrophilin

KW - complementarity-determining region

KW - gamma delta T cell

KW - ligand

KW - phosphoantigen

UR - http://www.scopus.com/inward/record.url?scp=85081225735&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2020.02.014

DO - 10.1016/j.immuni.2020.02.014

M3 - Article

C2 - 32155411

VL - 52

SP - 487-498.e6

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 3

ER -